Integrative Biobehavioral and Psychosocial Risk for Cognitive Decline in the Elderly PIs: Christopher G. Engeland & Jennifer E. Graham-Engeland PROJECT SUMMARY / ABSTRACT The incidence of cognitive impairment and Alzheimer?s dementia (AD) is rising rapidly as the world population is aging. The majority of past research to identify risk factors for dementia has focused on the predictive value of one factor at a time. This has resulted in a long list of factors which relate to cognitive decline and mild cognitive impairment (MCI), with little guidance as to which to prioritize or which targets might be most suitable for intervention. Our approach will address this problem by considering many factors simultaneously to help identify unique associations and provide a clearer description of how diverse psychological, behavioral, and physiological factors relate to cognitive decline. We focus on the role of three factors: negative and positive affect (mood), inflammation, and lipid profiles. A core hypothesis is that affect and inflammation profiles will explain, at least in part, the impact of diverse psychosocial and behavioral risk factors on cognitive decline and MCI. Our models will thus integrate key risk factors for cognitive decline that vary in daily life and which are associated with affect and inflammation ? social isolation, low physical activity, poor sleep, and physical pain ? in addition to genetic risk and covariates such as depression, demographics, diet, and medication use. We hypothesize that inflammation helps connect affect and lipid signaling with cognitive decline. To further improve our understanding of how different people vary, we will examine the degree to which cumulative life stress (lifetime adversity) modifies the associations between affect and inflammation with cognition, and will explore interactions with race/ethnicity. The proposed project will build on the Einstein Aging Study (EAS), which is recruiting a cohort of 500 community-residing men and women aged 70+ in the Bronx NY. Participants will complete 4 annual waves of data collection. Each wave will include a 14-day ?burst? of assessments, conducted up to 7x per day on smartphones to assess participants? experiences and behaviors in real life, as well as an annual in-depth neuropsychological assessment to determine cognitive function and incidence of cognitive impairment. Blood will be obtained before and after each 14-day burst to enable us to capture inflammatory load across the full two week burst; we will also quantify individuals? inflammatory responses in blood, which may be a more sensitive measure for the development of AD. Near the start of the study, we will perform an in-depth assessment of lifetime adversity and will also determine genetic risk for developing AD based on the ApoE gene. Known proteins in blood that relate to neurodegeneration will be quantified once per year. Such a comprehensive set of biomarkers has not been examined previously in longitudinal work to examine the role of psychosocial and behavioral factors on cognitive aging and impairment. Ultimately, this project holds great promise to 1) improve early detection for cognitive decline and AD; 2) identify individual variations in risk for AD; and 3) inform novel intervention approaches against cognitive aging, impairment, and eventual dementia.